HAIC vs. TACE plus sintilimab and bevacizumab for intermediate HCC with high tumor burden

Inclusion Criteria:

* Diagnosis: Histologically or cytologically confirmed hepatocellular carcinoma (HCC), or patients with cirrhosis meeting the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for HCC.
* Age: ≥ 18 years old.
* Performance Status: ECOG performance status score of 0.
* Prior Treatment: No prior systemic anti-tumor therapy or transarterial interventional therapy for HCC.
* Tumor Stage and Burden: Barcelona Clinic Liver Cancer (BCLC) Stage B, unsuitable for radical surgery and/or local therapy (such as ablation).
* Up-To-Seven Criteria: Tumor burden exceeding the Up-To-Seven criteria, defined as the sum of the size of the largest intrahepatic tumor (in cm) and the number of tumors being greater than 7.
* Tumor Distribution: Bilobar multifocal tumors.
* Measurable Disease: At least one measurable lesion with arterial phase enhancement on CT/MRI.
* Vascular Status: Patent portal vein with no evidence of portal vein tumor thrombus.
* Extrahepatic Status: No extrahepatic metastasis.
* Variceal Risk: No risk of variceal bleeding; esophagogastroduodenoscopy (EGD) within 6 months shows no gastroesophageal varices or active ulcers.
* Liver Function: Child-Pugh Grade A.
* Hematology: Platelets \> 75 × 10⁹/L; White Blood Cells \> 3.0 × 10⁹/L; Neutrophils \> 1.5 × 10⁹/L.
* Biochemistry: Serum bilirubin ≤ 1.5 × upper limit of normal (ULN); Transaminases ≤ 3 × ULN; Serum creatinine \< 1.5 × ULN.
* Physical Findings: No ascites
* Albumin ≥ 30 g/L.
* Coagulation: Normal coagulation function.
* Expectancy: Expected survival \> 3 months.
* Consent: Signed written informed consent and willingness/ability to comply with follow-up until death, study completion, or termination.

Exclusion Criteria:

* Histology: Known histology/cytology of fibrolamellar HCC, sarcomatoid HCC, or components of cholangiocarcinoma.
* Medical History: History of hepatic encephalopathy or liver transplantation.
* Effusions: Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage.
* Viral Hepatitis: Active Hepatitis B (HBV DNA \> 2000 IU/ml or 10⁴ copies/ml) or Hepatitis C (HCV RNA \> 10³ copies/ml); co-infection with both HBsAg and anti-HCV positive. (Eligible if levels drop below these criteria after nucleoside antiviral therapy) .
* Cardiovascular (Past 12 Months): Myocardial infarction, severe/unstable angina, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack), or pulmonary embolism.
* Ongoing Cardiac Issues: Arrhythmia ≥ Grade 2 (NCI-CTCAE); QTc prolongation (Male \> 450 ms, Female \> 470 ms).
* Bleeding Risk: History of gastrointestinal bleeding within 6 months or clear bleeding tendency (e.g., high-risk varices, active GI ulcer, persistent positive fecal occult blood).
* Hypertension: Uncontrollable hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg despite optimal treatment); history of hypertensive crisis or hypertensive encephalopathy.
* Organ Failure: Renal failure requiring hemodialysis or peritoneal dialysis; severe dysfunction of other major organs.
* Second Malignancy: History of other malignancies within 3 years prior to screening (except those with negligible risk of metastasis/death such as treated cervical cancer in situ, non-melanoma skin cancer, or localized prostate cancer).
* CNS Involvement: Known or new evidence of brain or leptomeningeal lesions. Coagulation Disorders: Hemophilia or bleeding tendency; currently taking therapeutic doses of coumarin derivatives (e.g., warfarin).
* Pregnancy/Lactation: Pregnant or breastfeeding females; women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
* Other History: Prior organ transplant; known HIV infection; active tuberculosis; allergy to chemotherapy drugs.
* Autoimmune Diseases: Active or history of autoimmune diseases (e.g., myasthenia gravis, myositis, autoimmune hepatitis, SLE, rheumatoid arthritis, IBD, etc.).
* General Compliance: Any serious acute/chronic physical or mental illness, or laboratory abnormalities that increase study risk or interfere with interpretation of results.
* Non-compliance: History of significant non-compliance with medical protocols or inability to provide reliable informed consent.